ArticleScientific reports2016
R-spondin 2 promotes acetylcholine receptor clustering at the neuromuscular junction via Lgr5.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Review
- Interplay between circadian rhythms, gut microbiota, and MASLD: from mechanistic foundations to therapeutic opportunities.Frontiers in medicine · 2026Review
- Synergic action of MicroRNAs and Wnts delivered by motor neuron EVs in promoting AChR clustering.Cell communication and signaling : CCS · 2025Article
- Calcitriol ameliorates motor deficits and prolongs survival of Chrne-deficient mouse, a model for congenital myasthenic syndrome, by inducing Rspo2.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review.International journal of molecular sciences · 2023Review
- RSPO3 is a novel contraction-inducible factor identified in an "in vitro exercise model" using primary human myotubes.Scientific reports · 2022Article
- Structure and Function of the Mammalian Neuromuscular Junction.Comprehensive Physiology · 2022Article
- Article
- Neuropilin 1 regulates bone marrow vascular regeneration and hematopoietic reconstitution.Nature communications · 2021Article
- Secreted Signaling Molecules at the Neuromuscular Junction in Physiology and Pathology.International journal of molecular sciences · 2021Review
- Characterization of rare spindle and root cell transcriptional profiles in the stria vascularis of the adult mouse cochlea.Scientific reports · 2020Article
- CTGF/CCN2 facilitates LRP4-mediated formation of the embryonic neuromuscular junction.EMBO reports · 2020Article
- Unveiling synapse pathology in spinal bulbar muscular atrophy by genome-wide transcriptome analysis of purified motor neurons derived from disease specific iPSCs.Molecular brain · 2020Article
- Myasthenia Gravis: From the Viewpoint of Pathogenicity Focusing on Acetylcholine Receptor Clustering, Trans-Synaptic Homeostasis and Synaptic Stability.Frontiers in molecular neuroscience · 2020Article
- Mianserin suppresses R-spondin 2-induced activation of Wnt/β-catenin signaling in chondrocytes and prevents cartilage degradation in a rat model of osteoarthritis.Scientific reports · 2019Article
- Differential effects of spinal motor neuron-derived and skeletal muscle-derived Rspo2 on acetylcholine receptor clustering at the neuromuscular junction.Scientific reports · 2018Article
- Lack of Fgf18 causes abnormal clustering of motor nerve terminals at the neuromuscular junction with reduced acetylcholine receptor clusters.Scientific reports · 2018Article
- Synaptic Homeostasis and Its Immunological Disturbance in Neuromuscular Junction Disorders.International journal of molecular sciences · 2017Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
At the neuromuscular junction (NMJ), acetylcholine receptor (AChR) clustering is mediated by spinal motor neuron (SMN)-derived agrin and its receptors on the muscle, the low-density lipoprotein receptor-related protein 4 (LRP4) and muscle-specific receptor tyrosine kinase (MuSK). Additionally, AChR clustering is mediated by the components of the Wnt pathway. Laser capture microdissection of SMNs revealed that a secreted activator of Wnt signaling, R-spondin 2 (Rspo2), is highly expressed in SMNs. We found that Rspo2 is enriched at the NMJ, and that Rspo2 induces MuSK phosphorylation and AChR clustering. Rspo2 requires Wnt ligands, but not agrin, for promoting AChR clustering in cultured myotubes. Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5), an Rspo2 receptor, is also accumulated at the NMJ, and is associated with MuSK via LRP4. Lgr5 is required for Rspo2-mediated AChR clustering in myotubes. In Rspo2-knockout mice, the number and density of AChRs at the NMJ are reduced. The Rspo2-knockout diaphragm has an altered ultrastructure with widened synaptic clefts and sparse synaptic vesicles. Frequency of miniature endplate currents is markedly reduced in Rspo2-knockout mice. To conclude, we demonstrate that Rspo2 and its receptor Lgr5 are Wnt-dependent and agrin-independent regulators of AChR clustering at the NMJ.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.